Methods of neutralizing IL-8 biological activity
One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.
1. A method for suppressing accumulation of IL-8 in an individual, which comprises administering an anti-IL-8 antibody to the individual, wherein the administered anti-IL-8 antibody comprises:
(a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:67,
(b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:73,
(c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:74,
(d) HVR-LI comprising the amino acid sequence of SEQ ID NO:70,
(e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:75, and
(f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:76.
2. The method of claim 1 , wherein the individual has elevated IL-8 levels.
3. The method of claim 1 , wherein the administered anti-IL-8 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:78 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:79.
4. The method of claim 1 , wherein the administered anti-IL-8 antibody comprises:
(a) a heavy chain comprising an amino acid sequence selected from: (i) SEQ ID NO:80; (ii) SEQ ID NO:81; (iii) SEQ ID NO:92; and (iv) SEQ ID NO:93;
(b) a light chain comprising the amino acid sequence of SEQ ID NO:82; or
(c) a heavy chain comprising an amino acid sequence selected from: (i) SEQ ID NO:80; (ii) SEQ ID NO:81; (iii) SEQ ID NO:92; and (iv) SEQ ID NO:93, and a light chain comprising the amino acid sequence of SEQ ID NO:82.
5. The method of claim 1 , wherein the administered anti-IL-8 antibody comprises:
(a) a heavy chain comprising the amino acid sequence of SEQ ID NO:80 and a light chain comprising the amino acid sequence of SEQ ID NO:82; or
(b) a heavy chain comprising the amino acid sequence of SEQ ID NO:81 and a light chain comprising the amino acid sequence of SEQ ID NO:82.
6. The method of claim 1 , wherein the administered anti-IL-8 antibody is an IgG antibody.
7. The method of claim 6 , wherein the administered anti-IL-8 antibody is IgG1, IgG2, IgG3 or IgG4.
8. The method of claim 7 , wherein the administered anti-IL-8 antibody is IgG1.
9. The method of claim 1 , wherein the administered anti-IL-8 antibody comprises one or more amino acid substitutions selected from: L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
10. The method of claim 9 , wherein the administered anti-IL-8 antibody comprises amino acid substitution N434A according to EU numbering.
11. The method of claim 9 , wherein the administered anti-IL-8 antibody comprises:
(a) amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering, or
(b) amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.